Fig. 1: Chronic stress promotes PLAGL2 expression via epinephrine.

a Molecular function of genes enriched in the PLAGL2 knockdown group (p < 0.05) and depressed (GSE9116 database, p < 0.05) patients, as determined by Gene Ontology enrichment analysis. b Schematic representation of the experimental design and timeline used to establish the chronic stress tumor mouse model. c Open field tests were used to assess the behaviors of chronic stress model mice (n = 6). d The tail suspension test was used to analyze the behaviors of chronic stress model mice (n = 6). e Body weights of the mice under stressed and nonstressed conditions (n = 6). f Tumor volumes of Hepa1-6 xenograft tumors in the model mice under control and stressed conditions (n = 6). g, h Images and weights of tumors from nonstressed and chronically stressed tumor model mice. i qRT‒PCR analysis of the mRNA expression of Zeb1, Zeb2, Twist1, Twist2, Snail, Slug, and PLAGL2 in tumor tissues from model mice under control and stressed conditions. j, k Western blot and quantitative analyses of the protein levels of EMT-related factors (N-cadherin and vimentin) and PLAGL2 in tumor tissues from mice under control and stressed conditions. l, m IHC and quantitative analyses of PLAGL2, Ki67, vimentin, and N-cadherin expression in tumor tissues from control and stressed mice. n, o Concentrations (Conc.) of Epi in the serum and tumor tissue of nonstressed and chronically stressed mice were measured by ELISA. The data are presented as the mean ± SD and were analyzed by two-tailed Student’s t tests. *p < 0.05, **p < 0.01, ***p < 0.01. Epi epinephrine.